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1.
J Hosp Infect ; 132: 20-27, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36521583

RESUMO

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) transmission is poorly defined. Previous studies have sampled air of rooms occupied by HIV-infected patients with PJP, while natural and direct exhalations of HIV-uninfected subjects remain under-investigated. Here, clinical facemasks were used to examine and quantify potential P. jirovecii exhalations from HIV-uninfected patients with suspected PJP and to determine whether pathogen exhalation was definable clinically or radiologically. METHODS: Forty-five patients in Leicester (England), highly suspected of having PJP based on European Conference on Infections in Leukaemia (ECIL-5) guidelines, each wore one facemask carrying a gelatine/PVA sampling matrix for 1 h while respiring normally. Mask contamination with P. jirovecii was assessed using a modified quantitative polymerase chain reaction targeting mitochondrial large subunit (MtLSU). Radiological findings on chest X-ray (CXR) and computed tomography (CT) were graded and analysed for correlation with P. jirovecii signals alongside relevant clinical and laboratory findings. RESULTS: P. jirovecii was detected in seven of 20 patients diagnosed with PJP and three of 19 patients with suspected but undiagnosed PJP. The median captured signal was 8.59 × 104 MtLSU copies/mask (interquartile range (IQR) = 3.01 × 105-1.81 × 104). Blood ß-D-glucan test results correlated with the mask detection data (r = 0.65; P<0.0001) but other clinical indices and radiological features did not. Five of the 10 P. jirovecii-exhalers exhibited normal CXR with a median exhalation burden 1.28 × 105 copies/mask (IQR = 1.51 × 105-2.27 × 104). Two P. jirovecii-exhalers (7.64 × 104 copies/mask) were asymptomatic. CONCLUSION: P. jirovecii was exhaled sufficiently during normal respiration to be detectable in facemasks worn by HIV-uninfected patients. Neither clinical nor radiological features correlated with P. jirovecii exhalation.


Assuntos
Infecções por HIV , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumocystis carinii/genética , Expiração , Máscaras , Pneumonia por Pneumocystis/diagnóstico , Infecções por HIV/complicações , Hospedeiro Imunocomprometido
2.
J Physiol Pharmacol ; 73(5)2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36942813

RESUMO

Ferroptosis is a cell death process caused by redox imbalance in the cell environment. However, the cell death pathway proves beneficial in anticancer therapy, so compounds inducing ferroptosis are sought. The paper presents a newly synthesized iron complex named FeT, composed of ferricyanide and tartrate, which seems to meet these expectations. It is relatively stable, easily soluble in water and capable of peroxidating unsaturated fatty acids. T24 bladder cells were used as model cells. Preliminary studies demonstrated a strong inhibitory effect of this compound on cell proliferation. The cytotoxicity of FeT was assessed. Independently, it initiates caspase activity, indicating the complex cellular impact of this compound. This effect is compellingly the result of FeT penetration into the cell's interior with possible direct damage to mitochondria, thus explaining the involvement of apoptosis in cell death. At the same time, after penetrating into the cell, it causes an increase in reactive oxygen species (ROS), lipid peroxidation and a decrease in reduced glutathione, which is interpreted as to cause ferroptosis. In turn, reducing mitochondrial potential may indicate both ferroptosis and an internal pathway to apoptosis.


Assuntos
Ferroptose , Ferro , Ferro/metabolismo , Apoptose , Espécies Reativas de Oxigênio/metabolismo , Peroxidação de Lipídeos , Ácidos Graxos/farmacologia
3.
Animal ; 15(1): 100045, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33516023

RESUMO

The current predation threat of domestic horses is generally low, and horses do not know predators' frightening cues. We studied whether horses still recognise predation threats. The aim of the study was to analyse the emotional response of purebred Arabian horses (Arabian) and Polish Konik horses (Konik) to an Arabian panther (Panthera pardus nimr) (panther) growl and a grey wolf (Canis lupus) (wolf) howl. Panther vocalisation was known to Arabian ancestors, whereas ancestors of Konik knew wolf vocalisation. The response to the howls of golden jackals (Canis aureus) (jackal), which did not prey on equids, was also studied comparatively. Two groups of 10 adult horses of each breed were subject to predator sounds of one predator daily for 5 min during a turn out on pasture. The test was performed for 18 days in total. The sound of each predator was interchangeably featured from one loudspeaker for 3 days followed by four loudspeakers simultaneously to imitate a group of predators for 3 days. The horses' emotional agitation in response to the sounds was measured based on the parameters of heart rate variability (HRV) using telemetric devices. The results showed that the predators' sounds were identified by horses as stressful or neutral. Horses generally retained their anti-predator responses even in the current habitat, which typically lacks predation cues. The results are not always coherent and may demonstrate that the response is somewhat attenuated. The wolf howl elicited a stronger response in Koniks. The panther growl more strongly influenced Arabians, whereas the jackal howl minimally elicited an agitation in the horses. The differentiated response of the two horse breeds to the three predator species suggests that the response is an innate adaptation to the predation risk in the habitat of the breed ancestors. This response occurs regardless of the emotional arousal specific to a breed, and the frightening cue is not the sound per se but the possible attack of predators. Horses display a type of understanding of the sound meaning. Their HRV response seems to be adequate for the threat signalised by the sound.


Assuntos
Lobos , Animais , Ecossistema , Frequência Cardíaca , Cavalos , Polônia , Comportamento Predatório
4.
Dalton Trans ; 47(30): 10213-10222, 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30014069

RESUMO

We report on the reactivity of R2P-P(Li)-PR'2 (R = tBu, iPr, R' = NEt2, iPr) towards diimido complexes [(dippN)2MCl2·dme] (M = Mo, W and dipp = 2,6-iPr2C6H3). A series of new complexes with diphosphanylphosphido ligands R2P-P-PR'2 were isolated. The solid-state structures of [(dippN)2M(Cl)(1,2-η-iPr2P-P-PiPr2)] (2Mo and 2W) and [(dippN)2M(Cl){1,2-η-tBu2P-P-P(NEt2)2}] (3Mo and 3W) were established by single-crystal X-ray diffraction analysis and indicate a side-on geometry of the R2P-P-PR'2 moiety. 3W and 3Mo are the first triphosphorus complexes with the amido ligand NEt2 on the P atom. [(dippN)2M(Cl)(1,2-η-tBu2P-P-PtBu2)] (1Mo and 1W) and 3Mo and 3W display similar side-on geometry in solution and in the solid state. By contrast, 2Mo and 2W reveal a dynamic behavior in solution. For the first time, the reactivity of diphosphanylphosphido complexes towards different nucleophiles was studied. The complexes react with the phosphorus nucleophile Ph2PLi, yielding phosphanylphosphinidene complexes [(dippN)2M(Cl)(η2-P-PR2)]- Li+ (M = Mo, W) together with related diphosphanes R'2P-PPh2. Carbon nucleophile MeLi does not yield [(dippN)2M(Cl)(η2-P-PR2)]- Li+ but substitutes a Cl ligand at the metal center. Moreover, we compare the coordination of the R2P-P-PR'2 moiety to different metal centers based on DFT methods.

5.
Pol J Vet Sci ; 21(4): 823-825, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30605294

RESUMO

This study analysed the influence of montelukast (MON; 10-8 - 10-4 M), a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist, on the contractility of the porcine uterine smooth muscle in the luteal phase of the oesterous cycle (n=8) and in early pregnancy (n=8). Stimulation of uterine strips in the luteal phase with MON has been shown to significantly reduce the amplitude of con- tractions, but not to affect the tension or frequency of contractions. A statistically significant tension increase and decrease in the frequency and amplitude of contractions was observed in pigs in early pregnancy. This suggests that MON has a different effect on the parameters under study in cyclic and pregnant pigs.


Assuntos
Acetatos/farmacologia , Antagonistas de Leucotrienos/farmacologia , Fase Luteal/fisiologia , Prenhez , Quinolinas/farmacologia , Suínos/fisiologia , Contração Uterina/efeitos dos fármacos , Animais , Ciclopropanos , Feminino , Gravidez , Sulfetos
6.
J Physiol Pharmacol ; 69(6)2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30898987

RESUMO

Pullulan and chitosan are biocompatible polysaccharides obtained from natural sources with many biomedical applications. Cationically modified polymers, such as chitosan and pullulan after covalent attachment of glycidyltrimethylammonium chloride (GTMAC), showed beneficial biological properties. In the present study, it was clearly demonstrated and confirmed that both cationically modified polysaccharides (chitosan-GTMAC and pullulan-GTMAC) have the antiatherosclerotic potential by inhibition of atherosclerotic plaque development and controlling the expression of genes involved in lipid metabolism. It has also been shown that the cationically modified chitosan (HTCC) at a dose of 200 mg/kg b.w./day in male apoE-knockout mice acted as hypolipidaemic agent. It was observed that a statistically significant decrease in low-density lipoprotein (LDL) cholesterol level by 32% occurred under the influence of HTCC at a dose of 200 mg/kg b.w./day after 16 weeks of the experiment compared to the control group of apoE(-/-) mice. Moreover, under the influence of cationically modified chitosan administered orally to female apoE-knockout mice at a dose of 300 mg/kg b.w./day for 18 weeks a statistically significant reduction by 33% in the area of atherosclerotic plaque was observed compared to the control group, i.e., apoE-knockout mice whose diet was not supplemented with the cationically modified polysaccharide. Current in vivo studies connected with cationically modified pullulan showed a statistically significant 22% reduction of the area of atherosclerotic plaque in the apoE(-/-) mice fed with a feed containing Pull-GTMAC at a dose of 500 mg/kg b.w./day for 18 weeks in comparison to the control group of apoE-knockout mice. In the in vitro studies it was also shown that cationically modified chitosan acted therapeutically by reduction of the level of the expression of human 3-hydroxy-3-methylglutaryl-CoA reductase (human HMG-CoAR) after 24 hours of incubation with HepG2 cells. However, cationically modified pullulan did not show this effect in the experiment on HepG2 cell line. On the other hand, Pull-GTMAC caused a statistically significant increase in insulin induced gene 1 (INSIG1) expression and increase in mRNA level of LDL receptor in brown fat tissue of female apoE-knockout mice after oral administration with feed at a dose of 300 mg/kg b.w./day for 18 weeks in comparison to the control group of apoE(-/-) mice, that was crearly demonstrated the effect of cationically modified pullulan on the expression of lipid metabolism genes in in vivo conditions. In the present article we have shown for first time that cationically modified pullulan and chitosan have some similarities in their antiatherogenic action but there are also some minor differences in mechanism of their effect on lipid metabolism.


Assuntos
Aterosclerose/tratamento farmacológico , Materiais Biocompatíveis/farmacologia , Quitosana/farmacologia , Glucanos/farmacologia , Placa Aterosclerótica/tratamento farmacológico , Polissacarídeos/farmacologia , Animais , Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placa Aterosclerótica/metabolismo , Receptores de LDL/metabolismo
7.
Pol J Vet Sci ; 20(3): 485-490, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29166277

RESUMO

The present in vitro study investigated the influence of doxazosin on the contractility of the urinary bladder in female pigs with experimentally induced cystitis. Fifteen juvenile female piglets (18-20 kg body weight) were randomly assigned into three groups (n=5 animals each): i) control (clinically healthy animals, without doxazosin treatment), ii) animals with induced inflammation of the urinary bladder, but without doxazosin treatment (experimental group I) and iii) animals with inflamed bladder, treated orally with doxazosin (0.1 mg/kg body weight for 30 days; experimental group II). Thereafter, the pigs were sacrificed and strips of the bladder trigone were suspended in organ baths. The tension and amplitude of the smooth muscles was measured before and after exposition to 5-hydroxytryptamine (5-HT; 10-6-10-4 M), acetylocholine (ACh; 10-5-10-3 M) and norepinephrine (NE; 10-9-10-7 M). 5-HT caused an increase in the tension of contractions in all the groups and the amplitude in the experimental groups, however, the effect was higher in the experimental group I than in group II as compared to that found in the pre-treatment period. ACh caused an increase in the tension in the control group and a decrease in the amplitude in both experimental groups; these changes significantly differed between the control and doxazosin-treated group. NE caused a decrease in the tension in both experimental groups and amplitude in all the groups, however, the effect was most strongly expressed in doxazosine-treated group. The present study has revealed that long-term administration of doxazosin causes a desensitization of the detrusor smooth muscle to in vitro applied mediators in the autonomic nervous system.


Assuntos
Cistite/veterinária , Doxazossina/farmacologia , Contração Muscular/efeitos dos fármacos , Doenças dos Suínos/induzido quimicamente , Acetilcolina/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Animais , Agonistas Colinérgicos/farmacologia , Cistite/induzido quimicamente , Feminino , Músculo Liso/efeitos dos fármacos , Norepinefrina/farmacologia , Distribuição Aleatória , Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Suínos , Doenças dos Suínos/tratamento farmacológico , Simpatomiméticos/farmacologia , Bexiga Urinária/efeitos dos fármacos
8.
Int J Neurosci ; 127(8): 709-715, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27671515

RESUMO

BACKGROUND: Homocysteine thiolactone (HTL) is a cyclic thioester of homocysteine (Hcy) contributing to the toxicity of this amino acid. HTL spontaneously reacts with protein lysine residues leading to altered properties of target proteins and induction of immune response. HTL is hydrolyzed to Hcy by plasma enzyme, paraoxonase 1 (PON1). Although both Hcy and PON1 may be involved in the pathogenesis of multiple sclerosis (MS), protein modification by HTL in this disease has not been studied so far. Purpose/Aim: The aim of this study was to assess the level of Hcy, HTL and autoantibodies against N-homocysteinylated proteins as well as PON1 activity in patients with MS. METHODS: The studies were performed in 61 MS patients with relapsing-remitting (RR group, n = 25) and secondary-progressive type of MS (SP group, n = 36), and in healthy people (C - control group, n = 44). RESULTS: Homocysteine level was significantly higher in MS patients comparing to control group (C vs. RR p < 0.01; C vs. SP p < 0.05). The level of HTL tended to be higher in RR-MS in comparison to control group, but it did not reach the level of significance. The level of antibodies against N-homocysteinylated proteins did not differ significantly between studied groups. PON1 activity was significantly lower in SP type of MS (SP vs. C p < 0.05; SP vs. RR p < 0.05). CONCLUSIONS: Although plasma Hcy concentration is higher in MS patients and PON1 activity is reduced in the SP form, MS is associated with minor or no changes in protein-attached HTL and anti-homocysteinylated protein immune response.


Assuntos
Homocisteína/análogos & derivados , Homocisteína/sangue , Esclerose Múltipla/sangue , Adulto , Arildialquilfosfatase/sangue , Biomarcadores/sangue , Proteínas Sanguíneas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Albumina Sérica
9.
J Physiol Pharmacol ; 67(5): 739-749, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28011954

RESUMO

Pullulan is a biocompatible polysaccharide obtained from black, yeast-like fungus Aureobasidium pullulans. This polymer is used to deliver various substances to the liver because of its specificity for this organ. Pullulan is internalized into hepatocytes in the process of asialoglycoprotein receptor mediated endocytosis. Recently, by reaction with glycidyltrimethylammonium chloride (GTMAC) we have successfully synthesized a cationically-modified pullulan (Pull-GTMAC). Pull-GTMAC exhibits some unique beneficial effects not found for its native counterpart. In this article we have reported for the first time that Pull-GTMAC administered orally to apoE-knockout mice (murine model of atherosclerosis) at a dose of 300 mg/kg b.w./day for 18 weeks showed anti-atherosclerotic activity reducing the area of atherosclerotic plaque. We have also found that Pull-GTMAC at a dose of 300 mg/kg b.w./day increases both the average daily mass of feces and the average number of droppings excreted by apoE(-/-) mouse in relation to the control sample derived from the mice fed with feed without the tested compound. However, the raw fat content in the feces of apoE-knockout mice was decreased in the group fed with the diet containing Pull-GTMAC towards control group of animals. Pull-GTMAC caused also statistically significant increase of mRNA level for LDL receptor in the apoE(-/-) mice liver after administration at a dose of 300 mg/kg/b.w./day for 18 weeks. However, the compound had no impact on lipid profile in serum of the tested mice. What is more, the studies on HepG2 cell line indicated an antiproliferative potential of cationically modified pullulan after 24 hour and 48 hour of incubation with the polysaccharide. In this paper we have shown for first time that cationically modified pullulan has antiatherogenic potential and influences on lipid metabolism.


Assuntos
Aterosclerose/metabolismo , Compostos de Epóxi/farmacologia , Glucanos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Animais , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Compostos de Epóxi/química , Compostos de Epóxi/uso terapêutico , Feminino , Expressão Gênica/efeitos dos fármacos , Glucanos/química , Glucanos/uso terapêutico , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/uso terapêutico , Receptores de LDL/genética
10.
Br Poult Sci ; 57(2): 219-26, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26955858

RESUMO

The aim of this study was to analyse the morphological lesion pattern of the heart of broiler chickens (Cobb 500, Hubbard F15 and Ross 308) during fattening with no clinical signs of disease and to determine the most susceptible period for the occurrence of morphological lesions. The most frequently diagnosed lesions in each genetic line were degeneration of the fibres with vacuolation, congestion of cardiac muscle, oedema and vacuolisation of the Purkinje cells. The highest numbers of morphological lesions were observed on d 38, 31 and 10 of life. The lesions were most numerous in the septum, followed by the left and right ventricles. Ischaemic cardiomyocytes were also most numerous on d 38 of life and in the left ventricle. Overload of cardiac muscle, prolonged hypoxia and increasing body weight on d 38 are the likely reasons for the largest number of lesions and ischaemic fibres, which may lead to heart failure.


Assuntos
Ascite/veterinária , Galinhas , Morte Súbita Cardíaca/veterinária , Miocárdio/patologia , Doenças das Aves Domésticas/patologia , Animais , Ascite/patologia , Cruzamento , Galinhas/crescimento & desenvolvimento , Morte Súbita Cardíaca/patologia , Fatores de Risco
11.
Minerva Cardioangiol ; 63(6): 577-86, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24743471

RESUMO

AIM: Remodeling and impaired blood flow in left atrial appendage (LAA), which occurs in patients with atrial fibrillation (AF), may lead to thrombus formation and possible thromboembolic complications. Although there are several pharmacological antithrombotic possibilities, some patients with several co-morbidities and contraindications to such treatment cannot be offered any of them. Therefore LAA closure systems may be an attractive alternative. We present our early experience with two currently available different LAA transcatheter closure systems (Watchman and Amplatzer Cardiac Plug). METHODS: Twenty three patients (mean age 69.1±6.8 years, 12 male) with non-rheumatic AF and high risk of thromboembolic complications (CHA2DS2-VASc score ≥2 (mean 4.5±1.5), who could not be treated with the long-term oral anticoagulation because of contraindications or significant side effects, were qualified to the LAA closure. RESULTS: The Amplatzer Cardiac Plug (St Jude Medical, St Paul, MN, USA) was implanted in 7 patients and Watchman Occluder (Boston Scientific, Boston, MA, USA) in the other 15 patients. The implantation was not performed in one patient as the transoesophageal echocardiography during the procedure revealed a new thrombus in LAA. The procedural details and follow-up data are presented. Neither severe pericardial effusion nor device related thrombus were observed. In long term follow-up transient ischemic attack was noted only in one patient (diagnosed with thrombophilia). One patient died 14 months after the procedure due to non-cardiac reason. CONCLUSION: The LAA occluder implantation seems to be a safe and reasonable alternative for oral anticoagulation and should be considered in patients with AF who have contraindications or complications of pharmacological treatment.


Assuntos
Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Dispositivo para Oclusão Septal , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia Transesofagiana , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Trombose/etiologia , Trombose/prevenção & controle
12.
Int Immunopharmacol ; 23(2): 558-67, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25448499

RESUMO

Scutellariae Radix (root of Scutellaria baicalensis) has a long history of application in traditional and in modern herbal medications. The major components of Scutellariae Radix are baicalin, baicalein, wogonoside and wogonin. Accumulating evidence demonstrates that Scutellaria has immunomodulatory effects and possesses compelling anticancer potential. Treatment of peripheral blood leukocytes (PBLs) with Scutellaria extract (SBE) enriched in baicalin, reduced viability of PBLs obtained from patients with acute lymphoblastic leukemia (ALL). SBE had no impact on the survival of healthy, control leukocytes. The immune system modulation by SBE resulted in increased production of IFNγ in PBLs, and reduced TNFα and IL-10 production in bone marrow cells (BMC), in ALL patients. SBE stimulated the nonspecific antiviral immunity, assessed by resistance of PBLs and BMC to vesicular stomatitis virus (VSV) infection. SBE showed pro-apoptotic activity in NALM-6 cell line (B-type human leukemia). The number of cells expressing annexin V increased from 6% in control cultures to 29% and 52% after treatment with 100 µg/ml and 200 µg/ml respectively. Increased percentage of apoptotic cells was observed when cells were treated with corresponding concentration of baicalin. SBE enhanced apoptosis of PBLs in BMC of leukemic children. The percentage of PBLs that underwent apoptosis and mean annexin V expression increased from 11% in the control to 17% and 24% for the doses of 100 µg/ml and 200 µg/ml respectively. Importantly, SBE did not induce apoptosis of PBLs in the healthy, control group.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Flavonoides/uso terapêutico , Imunidade Inata/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Scutellaria baicalensis/química , Adolescente , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Criança , Pré-Escolar , Efeito Citopatogênico Viral , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Flavonoides/isolamento & purificação , Humanos , Lactente , Leucócitos/imunologia , Leucócitos/patologia , Leucócitos/virologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Rhabdoviridae/efeitos dos fármacos
13.
J Physiol Pharmacol ; 65(6): 877-81, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25554992

RESUMO

Anti-atherogenic action of nebivolol in apolipoprotein E (apoE)-single knockout mouse model can be explained by its beneficial effect on endothelium, especially on endothelial nitric oxide synthase (eNOS). We, therefore, decided to use apoE and eNOS-double knockout mouse model to confirm that mechanism of nebivolol beneficial action. In apoE-single knockout mice, lesion area measured by "cross-section" of aortic roots was 79,244 ± 6,143 µm(2) in the control group versus 65,347 ± 6,152 µm(2) in nebivolol-treated group (P<0.05). However, in apoE and eNOS-double knockout mice, lesion area measured by "cross-section" of aortic roots was 92,319 ± 8,876 µm(2) in the control group versus 98,609 ± 9,164 µm(2) in nebivolol-treated group (P>0.05). The comparison between apoE-single knockout mice and apoE & eNOS-double knockout mice without treatment also showed statistically significant difference: 81,232 ± 8,264 µm(2) versus 92,319 ± 8,876 µm(2) (P<0.05). This is the first report that describes the effect of nebivolol on atherogenesis in apoE and eNOS-double knockout mice, proving directly the necessity of the presence of eNOS in endothelium for nebivolol to show its an anti-atherogenic potency.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Benzopiranos/farmacologia , Benzopiranos/uso terapêutico , Etanolaminas/farmacologia , Etanolaminas/uso terapêutico , Óxido Nítrico Sintase Tipo III/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Apolipoproteínas E/genética , Aterosclerose/sangue , Aterosclerose/patologia , Colesterol/sangue , Modelos Animais de Doenças , Feminino , Camundongos Knockout , Nebivolol , Óxido Nítrico Sintase Tipo III/genética , Triglicerídeos/sangue
14.
Acta Neurol Scand ; 127(6): e33-6, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22881373

RESUMO

OBJECTIVES: It has been implicated in many studies that reactive oxygen species play a role in the development of demyelination in multiple sclerosis (MS). Paraoxonase 1 (PON1) is an antioxidant enzyme that protects cell membranes against oxidative modification. Mitoxantrone is a cytotoxic drug approved for the treatment of MS with adverse effects associated potentially with an increased level of oxidative stress. The aim of this study was to assess the influence of mitoxantrone therapy on PON1 activity in patients with MS. METHODS: A studied group included 26 patients with secondary progressive MS, 16 women and 10 men. The blood was collected before the beginning of the therapy as well as after 6 and 12 months. Patients were receiving mitoxantrone every 12 weeks. Serum PON1 activity was assayed using two synthetic substrates: paraoxon and phenyl acetate. RESULTS: Paraoxonase 1 activity toward paraoxon and phenyl acetate and lipid profile did not change significantly in patients receiving mitoxantrone. CONCLUSIONS: Mitoxantrone therapy does not influence PON1 activity.


Assuntos
Antineoplásicos/uso terapêutico , Arildialquilfosfatase/metabolismo , Mitoxantrona/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/enzimologia , Adulto , Hidrolases de Éster Carboxílico/metabolismo , Estudos de Coortes , Esquema de Medicação , Feminino , Humanos , Masculino , Estresse Oxidativo
15.
Transgenic Res ; 22(3): 557-69, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23129482

RESUMO

The potato cyst nematode (Globodera rostochiensis) induces feeding sites (syncytia) in tomato and potato roots. In a previous study, 135 tomato genes up-regulated during G. rostochiensis migration and syncytium development were identified. Five genes (CYP97A29, DFR, FLS, NIK and PMEI) were chosen for further study to examine their roles in plant-nematode interactions. The promoters of these genes were isolated and potential cis regulatory elements in their sequences were characterized using bioinformatics tools. Promoter fusions with the ß-glucuronidase gene were constructed and introduced into tomato and potato genomes via transformation with Agrobacterium rhizogenes to produce hairy roots. The analysed promoters displayed different activity patterns in nematode-infected and uninfected transgenic hairy roots.


Assuntos
Raízes de Plantas/parasitologia , Regiões Promotoras Genéticas/genética , Solanum lycopersicum/genética , Solanum tuberosum/genética , Tylenchoidea/patogenicidade , Regiões 5' não Traduzidas , Animais , Clonagem Molecular , Sistema Enzimático do Citocromo P-450/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Células Gigantes/parasitologia , Glucuronidase/genética , Interações Hospedeiro-Parasita/genética , Raízes de Plantas/citologia , Raízes de Plantas/genética , Plantas Geneticamente Modificadas/genética , Solanum tuberosum/parasitologia
16.
Eur J Med Res ; 15 Suppl 2: 141-6, 2010 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-21147642

RESUMO

INTRODUCTION: TNF--α is one of the most important factors in the development and course of inflammation. It is suggested that polymorphism located in the 5'regulatory region of the TNF-α gene at position 308 (guanine [G]→adenine[A]) may increase the expression of this cytokine in fat tissue and influence the fat mass and insulin resistance. OBJECTIVE: To investigate whether the G-308A polymorphism of the TNF-α gene may influence obesity, insulin resistance, fasting plasma lipids, serum leptin levels, and the incidence of metabolic syndrome. MATERIAL AND METHODS: The obese group included 124 children with simple obesity (72 girls and 52 boys) aged 10-18 (mean age 15 years) with SDS of BMI ≥2.0. A control group consisted of 56 healthy non-obese children (36 girls and 20 boys) aged 11-18 (mean age 14 years) with SDS of BMI <1.0. Polymorphism identification was performed in total genomic DNA, using PCR-RFLP method. RESULTS: Carriers of A (AG+AA) allele among the obese children were significantly more frequent than in the control group (OR = 2.29, 95% CI 1.2-4.4, χ⊃2 = 6.24, P<0.05). Carriers of A alleles showed a higher concentrations of fasting glucose (81.3 ±10.5 vs. 77.4 ±10.3 mg/dl; P<0.05), but lower values of fasting insulin (15.1 ±7.3 vs. 19.0 ±9.5 µIU/ml; P<0.05), lower values of HOMA index (3.0 ±1.5 vs. 3.7 ±2.0; P <0.05). In the group of boys, carriers of A alleles showed a tendency for lower concentrations of HDL (43.8 ±12.6 vs. 48.3 ±11.8 mg/dl; P<0.05). Blood pressure and leptin level did not differ between the obese children with gene polymorphism and those of wild homozygous. The incidence of the full metabolic syndrome (MetS) in the children, according to the IDF definition, was 33%. The presence of the MetS in children with wild homozygous GG and carriers of A allele of TNF-α polymorphism gene did not show statistical differences (OR = 1.38; 95% CI 0.6-3.1, χ⊃2 = 0.58). CONCLUSIONS: 1/ Polymorphism G-308A of the TNF-α gene is more common in children with obesity; and 2/ Polymorphism G-308A of the TNF-α gene does not seem to be associated with the grade of obesity, insulin resistance, lipid profile, leptin levels, and the incidence of metabolic syndrome in obese children.


Assuntos
Síndrome Metabólica/etiologia , Obesidade/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Adolescente , Criança , HDL-Colesterol/sangue , Feminino , Genótipo , Humanos , Resistência à Insulina , Leptina/sangue , Masculino , Obesidade/sangue
17.
Cardiovasc Hematol Agents Med Chem ; 8(4): 173-86, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20545623

RESUMO

Apart from nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is the third gaseous mediator in mammals. H2S is synthesized from L-cysteine by cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), or by sequential action of alanine aminotransferase and 3-mercaptopyruvate sulfurtransferase. In the cardiovascular system, H2S is involved in the regulation of vascular tone and blood pressure, inhibits atherogenesis, and protects myocardium from ischemia-reperfusion injury. Recently, the first organic, water-soluble H2S donor, GYY4137, has been synthesized. In addition, H2S-releasing derivatives of several currently used drugs such as sildenafil, diclofenac, aspirin and mesalamine were obtained. Such compounds may be used in the future treatment of cardiovascular diseases. In this article, I describe the role of H2S in the regulation of blood pressure and in the pathogenesis of arterial hypertension and atherosclerosis which are two most common cardiovascular disorders.


Assuntos
Aterosclerose/metabolismo , Sulfeto de Hidrogênio/metabolismo , Hipertensão/metabolismo , Animais , Pressão Sanguínea , Líquidos Corporais/metabolismo , Humanos , Sulfeto de Hidrogênio/química , Camundongos , Ratos , Transdução de Sinais
18.
Pol J Vet Sci ; 12(3): 329-38, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19886254

RESUMO

The aim of the study was to monitor the effect of butaphosphane (1-(n-butylamino)-1-methylophosphorous acid) and cyanocobalamin (Catosal preparation, Bayer AG) on regeneration of the longissimus lumborum muscle (musculus longissimus lumborum) in pigs. Experiments were conducted on 34 piglets of Polish Large White breed with a mean body weight of 20 kg that were divided into two groups. Piglets of group I (control) received an intramuscular injection of 10 cm3 of 0.5% bupivacaine hydrochloride at both side of the spine. Piglets of group II were injected with bupivacaine, as in group I, and additionally received intramuscular injections of 5 ml of Catosal for 5 subsequent days. The animals were euthanized 6, 12, and 24 hours as well as 2, 3, 4, 5, 7, 10 and 14 days after muscle injury. Preparations obtained from muscle specimens were stained with HE, PAS method acc. to McManus, HBFP, Feulgen, and Unna methods. Ultrastructural preparations (TEM) were prepared following a standard procedure. The presence of vimentin, desmin and PCNA was detected immunohistochemically in sections prepared with a paraffin method. Necrosis of muscle fibres was observed in all animals after bupivacaine injection. The administration of Catosal accelerated the regeneration of damaged skeletal muscles in pigs through the facilitation of phagocytosis and enhancement of myogenic cells proliferation. No effect of Catosal was found on differentiation of myoblasts or maturation of newly-formed muscle fibres.


Assuntos
Fibras Musculares Esqueléticas/efeitos dos fármacos , Doenças Musculares/veterinária , Necrose/veterinária , Compostos Organofosforados/farmacologia , Doenças dos Suínos/tratamento farmacológico , Vitamina B 12/farmacologia , Animais , Bupivacaína/efeitos adversos , Doenças Musculares/induzido quimicamente , Doenças Musculares/tratamento farmacológico , Necrose/induzido quimicamente , Necrose/tratamento farmacológico , Organofosfonatos , Suínos , Doenças dos Suínos/induzido quimicamente
19.
J Appl Microbiol ; 106(1): 268-77, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19054227

RESUMO

AIMS: Dickeya zeae is a pectinolytic bacterium responsible for soft rot disease in flower bulb crops. In this study, the possibility of controlling soft rot disease in hyacinth by using antagonistic bacteria isolated from hyacinth bulbs was explored. METHODS AND RESULTS: Bacterial isolates with potential for biocontrol were selected on the basis of antibiosis against D. zeae, siderophore production, and the N-acyl homoserine lactones (AHLs)-inactivation. In in vitro assays, 35 out of 565 hyacinth-associated bacterial isolates produced antimicrobial substances against D. zeae, whereas 20 degraded AHLs, and 35 produced siderophores. Isolates of interest were identified by 16S rDNA sequence analysis and reaction in BIOLOG tests. Twenty-six isolates that differed in characteristics were selected for pathogenicity testing on hyacinth cultivars, Pink Pearl and Carnegie. Two strains identified as Rahnella aquatilis and one as Erwinia persicinus significantly reduced tissue maceration caused by D. zeae 2019 on hyacinth bulbs, but not on leaves. CONCLUSIONS: Hyacinth bulbs harbour bacteria belonging to different taxonomic groups that are antagonistic to D. zeae, and some can attenuate decay of bulb tissue. SIGNIFICANCE AND IMPACT OF THE STUDY: Selected hyacinth-associated bacterial isolates have potential for control of soft rot disease caused by D. zeae in hyacinth bulb production.


Assuntos
Antibacterianos/farmacologia , Antibiose , Eichhornia/microbiologia , Controle Biológico de Vetores/métodos , Doenças das Plantas/microbiologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/análise , Antibacterianos/isolamento & purificação , Antibiose/genética , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Hidrolases de Éster Carboxílico , Enterobacteriaceae/isolamento & purificação , Raízes de Plantas/genética , Raízes de Plantas/microbiologia , RNA Ribossômico 16S/genética , Sideróforos/análise
20.
Mult Scler ; 15(3): 399-402, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18845659

RESUMO

BACKGROUND: Paraoxonase 1 (PON1) is an antioxidant enzyme bound to plasma high-density lipoproteins and is also present in the brain. OBJECTIVE: The aim of this study was to estimate the activity of PON1 in patients with different types of MS. METHODS: The PON1 activity toward paraoxon and phenyl acetate and lipid profile was examined in 40 relapsing-remitting (RR) patients in relapse, in 42 RR patients in remission, in 55 progressive MS patients and in 40 healthy individuals. RESULTS: PON1 activity did not differ in MS patients compared to control group. PON1 activity in relapse was significantly lower in comparison to the other MS groups. Hypercholesterolemia was observed in MS patients. CONCLUSION: PON1 activity does not change in the course of stable and progressive type of MS and is decreased by the relapse of MS.


Assuntos
Arildialquilfosfatase/sangue , Esclerose Múltipla Crônica Progressiva/metabolismo , Esclerose Múltipla Recidivante-Remitente/metabolismo , Adulto , LDL-Colesterol/sangue , Ativação Enzimática , Feminino , Humanos , Hipercolesterolemia/metabolismo , Lipoproteínas HDL/metabolismo , Masculino , Paraoxon/metabolismo , Fenilacetatos/metabolismo , Triglicerídeos/metabolismo
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